The molecular test identifying the hMSH2 and hMLH1 genes, whose mutations lead to the development of hereditary nonpolyposis colon cancer (HNPCC), has only recently become available. HNPCC, which accounts for approximately 5% of all colorectal cancers (CRC), can now serve as a prototype for the development of genetic counseling protocols for hereditary cancer where effective forms of surveillance for early detection exist. Equally important, the psychosocial and behavioral aspects and sequelae of such counseling can be assessed over the short- and long-term, and adherence to surveillance recommendations measured. important information on willingness to undergo testing, the impact of risk identification on individuals and families, and effective ways to provide psychosocial support for those counseled is now lacking. In order to address this challenge, we have assembled a multidisciplinary team of investigators from medicine, psychiatry and psychology, medical and molecular genetics, epidemiology and public health, biostatistics, and cancer prevention. The proposed investigation will study a consecutive series of approximately 1,000 index cases of CRC, identified at the UTMDACC, who will be offered molecular testing for HNPCC and participation in our prospective study. From this series, we expect to enroll approximately 65 carriers of HNPCC mutations, and 225 first degree relatives (FDRs) of those index cases. Spouses of FDRs (c.100) also will be enrolled in the psychosocial portion of the study. Finally, we will follow a sample of noncarrier index cases for psychosocial assessment in order to have carriers and noncarriers at all levels of the design. All participants will be studied prospectively and will be assessed at baseline (enrollment), within two weeks after notification of molecular test results (for relevant subjects), and 3, 6 and 12 months later. A conceptual model that integrates leading social and cognitive/behavioral theoretic perspectives, featuring the stages of change and an adherence prediction framework, will guide the selection of variables, instruments and analyses. The instrument battery will, in large part, consist of carefully selected standardized tests of psychologic functioning, personality style, coping behavior, marital adjustment, social support, stage of change (readiness to engage in molecular testing and surveillance) and relevant knowledge, attitudes and beliefs about CRC, risk perception, and early detection. Major end points of the study will include completion of molecular testing; adherence to surveillance recommendations among carrier and noncarrier FDRs; and psychosocial indicators of distress and well-being. The study population will be enriched by the inclusion of families in the UTMDACC Hereditary Colon Cancer Registry (40 families) which contains approximately 28 index cases and 77 FDRs. Registry families will participate in focus groups, protocol development and testing, instrument development and pilot studies. Four pilot studies will address important qualitative issues: a telephone "counseling line" to deal with questions, concerns and problems; audiotaped counseling sessions as an educational intervention; process analysis of counseling sessions; and field trips to registry families to study family dynamics in risk notification and genetic counseling.